Multiple Sclerosis is the most common demyelinating disease of the central nervous system. MS is considered to be an autoimmune disease that is triggered by an environmental agent, most likely a pathogen. Destruction of oligodendrocytes and loss of integrity of the underlying axons, form the core pathologic features of MS. Apoptotic death of oligodendrocytes, also referred to as primary oligodendrogliopathy, is seen in approximately 40% of MS lesions and is believed to be the cause of progressive neurological disability. There is considerable need to develop a model of primary oligodendrogliopathy, since this type of destruction of oligodendrocytes is not amenable to conventional therapies. We also need to develop appropriate neuroimaging strategies that can distinguish and quantify inflammatory and non-inflammatory mechanisms of demyelination. We plan to examine a novel model of primary oligodendrogliopathy which is induced by the injection of LPS into CNS white matter. We propose that this model more likely represents the underpinnings of CNS demyelination in the prototypic type III lesion. This model of CNS demyelination will provide an opportunity to examine the sensitivity of a range of established and novel MRI techniques to distinguish inflammatory and non-inflammatory pathways and examine the efficacy of neuroprotective agents in blunting the progression of the non- inflammatory demyelinating lesions. This study opens the way to examine the loss of myelin in the brain using novel MRI techniques. Also, it explores the use of new drugs to prevent and reverse myelin injury. [unreadable] [unreadable] [unreadable]